In 1995 we developed the capability to produce infectious respiratory syncytial virus (RSV) by the intracellular coexpression of five cDNAs encoding a (i) complete version of RSV replicative intermediate RNA (antigenome) and (ii) the four RSV proteins that we showed were necessary and sufficient to produce nucleocapsids competent for transcription and RNA replication, namely the N, P, L and M2 ORF1 proteins. The ability to produce RSV from cDNA establishes the first available method for the direct engineering of this important, uncontrolled pathogen. An important use will be to construct live attenuated viruses as vaccines. One strategy will be to characterize and combine mutations from existing attenuated viruses which were produced by the standard method of chemical mutagenesis of virus suspensions. Extensive evaluation of these existing viruses in experimental animals and human volunteers suggests that the strategy of using an attenuated virus for RSV immunoprophylaxis will be successful, but that the existing viruses might not be satisfactorily attenuated. The ability to fine-tune the level of attenuation (and possibly genetic stability) by manipulating and combining individual mutations should make it possible to produce appropriately-attenuated vaccine viruses to order. This also will make it possible to modify vaccine virus to accommodate antigenic drift in circulating virus. A second strategy will be to continue a detailed characterization of RSV molecular genetics with the idea that novel methods of attenuation or vaccine improvement will be uncovered. In addition, it is possible that the level of immunity associated with natural infection might be improved quantitatively or qualitatively by the inclusion in recombinant RSV of cytokine genes or additional T cell epitopes, by ablation of possible epitopes associated with reactogenicity, or by other manipulations.